Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs

Ivan Vannini, Petra M. Wise, Kishore B. Challagundla, Meropi Plousiou, Mirco Raffini, Erika Bandini, Francesca Fanini, Giorgia Paliaga, Melissa Crawford, Manuela Ferracin, Cristina Ivan, Linda Fabris, Ramana V. Davuluri, Zhiyi Guo, Maria Angelica Cortez, Xinna Zhang, Lu Chen, Shuxing Zhang, Cecilia Fernandez-Cymering, Leng HanSilvia Carloni, Samanta Salvi, Hui Ling, Mariam Murtadha, Paolo Neviani, Barbara J. Gitlitz, Ite A. Laird-Offringa, Patrick Nana-Sinkam, Massimo Negrini, Han Liang, Dino Amadori, Amelia Cimmino, Muller Fabbri, George A. Calin

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p,-663b-3p, and-95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.

Original languageEnglish (US)
Article number1801
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Vannini, I., Wise, P. M., Challagundla, K. B., Plousiou, M., Raffini, M., Bandini, E., Fanini, F., Paliaga, G., Crawford, M., Ferracin, M., Ivan, C., Fabris, L., Davuluri, R. V., Guo, Z., Cortez, M. A., Zhang, X., Chen, L., Zhang, S., Fernandez-Cymering, C., ... Calin, G. A. (2017). Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs. Nature communications, 8(1), [1801]. https://doi.org/10.1038/s41467-017-01562-9